Induction of tolerance to human factor VIII in mice
Open Access
- 15 May 2001
- journal article
- Published by American Society of Hematology in Blood
- Vol. 97 (10) , 3311-3312
- https://doi.org/10.1182/blood.v97.10.3311
Abstract
This paper reports loss of human factor VIII (hFVIII) inhibitory antibody in immunocompetent C57BL/6 mice. High-titer anti-hFVIII antibody developed in the mice within 7 to 14 days of intraportal administration of adeno-associated virus (AAV) carrying FVIII that coincided with a reduction in plasma hFVIII antigen. Bethesda titers (> 100 units) persisted relatively unchanged for 9 to 10 months. Unexpectedly, at 10 months after injection of the virus, hFVIII protein (up to 59 ng/mL) was detected in 3 mice at the same time as disappearance of hFVIII inhibitor. The level of hFVIII was similar to that found in immunodeficient mice receiving the same dose of recombinant AAV carrying hFVIII without hFVIII inhibitor. These results suggest that tolerance to hFVIII can be induced by sustained expression of hFVIII in a mouse model. Further elucidation of this observation may affect use of FVIII gene transfer in the treatment of inhibitor-positive patients with hemophilia A.Keywords
This publication has 14 references indexed in Scilit:
- Persistent expression of canine factor IX in hemophilia B caninesGene Therapy, 1999
- Advances toward Gene Therapy for Hemophilia at the MillenniumHuman Gene Therapy, 1999
- Long-term expression of human coagulation factor VIII and correction of hemophilia A after in vivo retroviral gene transfer in factor VIII-deficient miceProceedings of the National Academy of Sciences, 1999
- Recombinant factor VIIa for patients with inhibitors to factor VIII or IX or factor VII deficiencyHaemophilia, 1999
- Use of prothrombin complex concentrates and activated prothrombin complex concentrates as prophylactic therapy in haemophilia patients with inhibitorsHaemophilia, 1999
- Molecular Biological Aspects of Inhibitor DevelopmentVox Sanguinis, 1999
- Protocols, Dosages and Clinical Aspects of Immune ToleranceVox Sanguinis, 1996
- Factor VIII Inhibitors in Patients with Hemophilia A: Epidemiology of Inhibitor Development and Induction of Immune Tolerance for Factor VIIISeminars in Thrombosis and Hemostasis, 1995
- Incidence of development of factor VIII and factor IX inhibitors in haemophiliacsThe Lancet, 1992
- The Use of Porcine Factor VIII Concentrate (Hyate:C) in the Treatment of Patients With Inhibitor Antibodies to Factor VIIIArchives of internal medicine (1960), 1989